Alemtuzumab vs. Interferon β -1a in Early Multiple Sclerosis 1

1. Safety and Side Effects • Patients experienced slightly more adverse events on alemtuzumab than interferon. This was almost entirely due to the mild or moderate symptoms associated with the infusion of alemtuzumab, typically headache and rash, which were controllable with simple measures. • Infections were more common in the alemtuzumab group, however this was predominantly due to increased respiratory tract (upper and lower) infections rather than more serious opportunistic infections. Malignancy was balanced between the treatment arms; after the study period in the alemtuzumab group there was a single case of leukaemia. • The significant (common and potentially severe) complication of alemtuzumab treatment was autoimmunity. This was most frequently treatable hyper/hypo-thyroidism and less commonly immune thrombocytopaenic purpura (ITP). For one patient the ITP was fatal. Alemtuzumab vs. Interferon β-1a in Early Multiple Sclerosis1 Figure 1 Addenbrooke’s Clinical Research Centre • Introduction • Multiple sclerosis (MS) is thought to be an autoimmune disease in which aberrant immune responses led by focal lymphocytic infiltrations cause damage of myelin and axons. It is the commonest potentially disabling disease of the central nervous system in the Western World. • Alemtuzumab is a monoclonal antibody, humanised to reduce the potential for patients to develop an immune response against it, that targets CD52 on lymphocytes and monocytes. It is currently licensed for the treatment of B-CLL and has been studied in patients with multiple sclerosis at Cambridge since 1991. • This multicentre phase 2, randomised, rater blinded trial was of previously untreated patients with early relapsing-remitting multiple sclerosis. Disease activity was confirmed clinically (two or more relapses in the preceding 2 years) and radiologically (one or more enhancing lesions on cranial magnetic resonance imaging). • The control group was actively treated with interferon-β. Two dose regimens of alemtuzumab were tested; there was no difference between the two doses in the safety or outcome measures, so the alemtuzumab data are pooled. Figure 2 Conclusions In early, untreated, relapsing-remitting multiple sclerosis compared to interferon: Alemtuzumab suppresses relapse rate by 74% figure1 Alemtuzumab reduces the rate of fixed disability by 74% figure2 Alemtuzumab improves mean disability figure3 As previously described, adverse effects of alemtuzumab are infusion reaction infections and autoimmunity Phase 3 studies of alemtuzumab are currently enrolling Figure 3 University of Cambridge Neuroscience 1. The CAMMS223 Trial Investigators Alemtuzumab vs. Interferon Beta-1a in Early Multiple Sclerosis The New England Journal of Medicine Vol. 359:1786-1801 (October 23, 2008) Poster prepared by T Button on behalf of CAMMS223 Trial Investigators: PI AJ Coles, PI DAS Compston